The present invention relates to the culture of microorganisms in a sealed vessel in which they are kept in suspension in nutrient substrate solution that is aerated with oxygen-containing gas.
The submerged culture microorganisms are generally kept in suspension in a liquid nutrient solution in which the parameters on which growth is dependent, such as the pH value, the oxygen concentration and others, are carefully controlled. For the optimum supply of the microorganisms suspended in the nutrient solution with substances essential for growth, such as a source of carbon, salts, vitamins, trace elements and oxygen and for the removal of the products of microbiological metabolism, it is necessary to maintain certain specific culture conditions, that is to say an intensive mixing of the nutrient substrate solution in order to obtain a homogeneous distribution of the phases, a high gas-liquid mass exchange rate and a good distribution of the gas phase. Furthermore, there has to be an efficient way of conducting away the heat produced. In this connection the wording homogeneous distribution is used in the sense of not only homogenization (the normal sense of the wording) of the dissolved substrate components in the vehicle phase (normally water), but furthermore it is used in the sense of a complete suspension of each and every microorganism in the
nutrient solution.
In connection with the culture of microorganisms in vessels certain troubling conditions are likely in the day-to-day operation of the plant inasfar as the microorganisms frequently have the tendency of building up densely packed layers on the wall of the reactor, this causing on the one hand an improverishment of the nutrient substrate solution with respect to active microorganisms and on the other hand a loss in productivity or drop in product quality, because the microorganisms forming the layer on the wall will only get a limited supply of nutrients. Acting on the notion that flow conditions in the culture vessel have been the main cause of decreased growth of the microorganisms, attempts have been made in the past to overcome this undesired effect by producing a higher degree of turbulence in the culture vessel. Although it has in fact been possible for good effects to be produced when working on a small scale, that is to say under lab conditions with a 5 to 200 liter vessel, inasfar as there was then much less wall-adherent growth, the scaling up of the process with turbulent nutrient flow to the size of vessels normally used in regular production plant, that is to say with a capacity of 10,000 to 50,000 liters, has not been possible without serious shortcomings. This is because on the one hand the power necessary for the agitating or stirring effect went up in proportion to the volume of the vessel and, on the other hand there was some trouble experienced in conducting away the heat produced by agitation and the sizeable amount of heat of reaction caused by aerobic bioprocesses, if the plant was to be run at a low culture temperature. Furthermore, attempts have been made at putting an end to the formation of dead zones in which there is no or hardly any mixing effect in the nutrient substrate solution by causing a carefully controlled and defined circulation of the suspension throughout the volume of the vessel. However, on testing under working conditions there was seen to be the shortcoming that a high specific drive power was needed and that the gas phase was not homogeneously divided up and distributed so that there was less growth of the microorganisms.
In the prior art, microorganisms have furthermore been aerobically cultured in a fermenter designed as a so-called toroidal reactor. Such a fermenter was made up of a hollow torus in which the nutrient substrate solution was kept circulating by a tangential agitator and gas was supplied thereto. Although the specific drive power needed for operation of this fermenter was relatively low, trouble was caused by premature segregaton of gas so that there was a tendency for the supply of oxygen not to be high enough.